PXD029937

PXD029937 is an original dataset announced via ProteomeXchange.

Title	Effects of recombinant α1-microglobulin on early proteomic response in risk organs after exposure to 177Lu-octreotate
Description	Introduction: Recombinant α1-microglobulin (A1M) is a proposed radioprotector during 177Lu-octreotate treatment of neuroendocrine tumors. Treatment with 177Lu-octreotate is currently limited by bone marrow and renal toxicity. Co-administration of 177Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue while allowing higher absorbed doses to the tumor tissue. However, the mechanisms underlying the protective effects of co-administration of 177Lu-octreotate and A1M are still not fully understood. The aim of this study was to examine the proteomic response of mouse kidneys and bone marrow short time after 177Lu-octreotate and/or A1M administration. Methods: C57/6N mice (n=5/group) were injected with 150 MBq 177Lu-octreotate and/or A1M (5 mg/kg). Corresponding control mice (n=5/group) were injected with saline or the A1M vehicle solution. The animals were killed at 24 hours or 7 days post injection, followed by collection of bone marrow, kidney medulla, and kidney cortex samples at resp. time-points. One of the kidneys from each mouse was used for dosimetric assessment by measuring the 177Lu activity concentration in a gamma counter. Differential protein expression was analyzed with tandem mass spectrometry (LC-MS/MS). Ingenuity Pathway Analysis was then used to simulate affected canonical pathways, upstream regulators, and toxicity functions for identified proteins with |fold change| ≥ 1.5. Results: PHLDA3 was the most prominent radiation responsive protein found in kidney tissue. In general, no statistically significant difference in the expression of radiation-related proteins was observed between the 177Lu-octreotate and the 177Lu-octreotate+A1M groups. Several canonical pathways were identified in bone marrow, with the majority found in the 177Lu-octreotate+A1M group. Although toxicity functions related to nephrotoxicity were identified in kidney tissue in all groups, the predicted state (activated or inhibited) of these functions could not be determined. Conclusions: These findings demonstrated a tissue-dependent proteomic response following exposure to 177Lu-octreotate alone or together with A1M. Combining 177Lu-octreotate with A1M did not seem to inhibit the radiation induced expressions, short time after exposure. Long term effects of the combination of A1M and 177Lu-octreotate needs to be further studied.
HostingRepository	PRIDE
AnnounceDate	2026-02-23
AnnouncementXML	Submission_2026-02-22_20:28:16.554.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Proteomics Core Facility
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; methylthiolated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-26 03:24:18	ID requested
⏵ 1	2026-02-22 20:28:17	announced

10.3390/ijms25137480;

Ytterbrink C, Shubbar E, Parris TZ, Langen B, Druid M, Sch, ü, ler E, Strand SE, Å, kerstr, ö, m B, Gram M, Helou K, Forssell-Aronsson E, Lu-Octreotate. Int J Mol Sci, 25(13):(2024) [pubmed]

ProteomeXchange project tag: Human Proteome Project

submitter keyword: proteomics, radio-protector, LC-MS, kidney, 177Lu-octreotate,Alpha-1-microglobulin

Carina Sihlbom
contact affiliation	Proteomics Core facility University of Gothenburg Sweden
contact email	carina.sihlbom@gu.se
lab head
Proteomics Core Facility
contact affiliation	SAMBIO Core Facilities, Sahgrenska Academy, University of Gothenburg
contact email	gupcf@outlook.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029937
     1. Label: PRIDE project
     2. Name: Effects of recombinant α1-microglobulin on early proteomic response in risk organs after exposure to 177Lu-octreotate